PB2017: CLINICAL OUTCOMES BY SF3B1 MUTATION STATUS IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES RETREATED WITH ERYTHROPOIESIS-STIMULATING AGENTS
Authors: Guillermo Garcia-Manero, Rayna K. Matsuno, Ali Mcbride, Adeola Y Makinde, Thomas D. Brown, Danny Idryo, Ronda Broome, Autumn Herriman, Kristiana Wilkinson, Sheetal Walters, Andrew Schrag, Hina Mohammed, Monika A. Izano, Sudipto Mukherjee
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: Patients with SF3B1-mutated lower-risk myelodysplastic syndromes (LR-MDS) often have a more favorable prognosis versus those with SF3B1 wildtype. A sizeable number of patients with LR-MDS undergo erythropoiesis-stimulating agent (ESA) treatment even after experiencing ESA failure in first line. Aims: This study evaluated the outcomes of patients with LR-MDS retreated with ESAs in routine clinical practice, stratified by SF3B1 status. Methods: This retrospective cohort study included patients with LR-MDS in the US community setting who initiated ESAs as first-line therapy between January 1, 2016 and June 30, 2019, and were followed through June 30, 2021. Eligible patients discontinued ESAs (treatment gap ≥ 3 weeks for epoetin alfa or ≥ 6 weeks for darbepoetin alfa) and subsequently reinitiated ESA therapy at least once during follow-up. Ring sideroblasts (RS) ≥ 15% served as a surrogate for patients with unknown SF3B1 mutation status. Outcomes included ESA switches, dose reductions and escalations, ESA failure, and overall survival (OS). Primary ESA failure was defined as no rise in hemoglobin (Hb) ≥ 1.5 g/dL or no decrease in RBC transfusion requirement by 8 weeks of treatment. Transfusion-dependent (TD) status was evaluated for patients who were transfusion independent (TI) at baseline. Results: A total of 82 patients with LR-MDS and repeat ESA treatment were included. Median age at start of ESA treatment was 79 years (interquartile range [IQR], 72–85). Diagnosis of MDS-RS, MDS with isolated del(5q), MDS with multilineage dysplasia, and MDS with single lineage dysplasia was reported in 30 (36%), 7 (9%), 9 (11%), and 9 (11%) patients, respectively; 27 (33%) had unknown classification. Median follow-up was 26 months (IQR, 13–38) with 65% failing ESA therapy by 8 weeks. Table shows patients’ SF3B1 mutation status, median OS, patients who had an ESA switch, dose reduction or escalation, experienced ESA failure, and patients who were TI at baseline and became TD during follow-up. Results were similar when RS was not used as a surrogate, and when analyses were limited to patients who were treated with ESAs only throughout follow-up. Summary/Conclusion: In this study of patients with LR-MDS retreated with ESAs, primary ESA failure was high with nearly half of TI patients becoming TD during follow-up. OS was poor regardless of SF3B1 status – 2–4 times lower than the remaining life expectancy for a 79-year-old (108 months for men; 125 months for women). Although treatment options were limited during the study period, the high primary failure rate suggests that patients with LR-MDS may benefit from alternatives to ESAs.© 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved. Keywords: Survival, Real world data, Erythropoieisis, Myelodysplastic syndrome